The present invention relates to TKR459, which is an antibiotic of use as a therapeutic agent for fungal infectious diseases, a method for their production, and microorganisms producing said antibiotic.
Fungi are known to cause a variety of infectious diseases in man, animals, and plants. In man, for instance, they cause superficial mycosis affecting the skin, oral cavity, etc. and systemic mycosis affecting the viscera, brain, etc. They cause similar infections in pet and domestic animals as well. Furthermore, fungi inflict various hazardous effects on plants such as orchard trees and vegetables.
As the principal pathogenic fungi causing systemic mycosis in man, those of the genera Candida, Cryptococcus, and Aspergillus, among others, are known. As to superficial mycosis, Candida species affecting the skin, oral cavity, and vagina and Trichophytons infecting the skin of the extremities are regarded as the major pathogenic fungi. Besides those fungi, many other fungi exist in the environment and are suspected to contaminate the animal and vegetable kingdoms.
As antimycotics of use for the prevention and treatment of such fungal infections and contaminations, only a very few are known. Among them, as therapeutic drugs for systemic mycosis in man and animals, for instance, amphotericin B, flucytosine, miconazole, and fluconazole can be mentioned. However, those compounds are not fully satisfactory in potency, toxic potential, or antifungal spectrum, thus being not impeccable as therapeutic drugs.
In view of the above-mentioned prior art, the present invention has for its object to provide a novel antibiotic which is of value as a therapeutic agent for fungal infections.
In their search for a novel antibiotic, the inventors of the present invention isolated a large number of microorganisms from the natural kingdom, isolated the antibiotics they produced, and scrutinized their biological properties. As a result, they discovered that the culture broth of a strain of microorganism of the class Fungi Imperfecti contained an antibiotic having antifungal activity against pathogenic fungi inclusive of Candida albicans, Candida kefyr, and Cryptococcus neoformans. Accordingly the inventors isolated this antibiotic and studied its physicochemical properties. As a result, they discovered that the above antibiotic is a novel substance having distinct physicochemical characteristics and named it TKR459.
The present invention, therefore, is directed to the novel antibiotic TKR459 which is represented by the following chemical formula (1), or its pharmacologically acceptable salt. 
The present invention is further directed to a method of producing the antibiotic TKR459 which comprises culturing a strain of microorganism belonging to Fungi Imperfecti and capable of elaborating said antibiotic TKR459 and then isolating said substance from the resulting culture broth.
Furthermore, the present invention is directed to a microorganism belonging to Fungi Imperfecti and capable of producing the antibiotic TKR459.